Increasing evidence indicates that circulating antigen-antibody complexes play a role in the pathogenesis of a variety of dermatologic, rheumatologic, neoplastic and infectious disease states. We have identified and partially characterized the immune complexes which exist in several diseases, i.e. Sjogren's syndrome, mixed cryoglobulinemia mixed connective tissue disease, acute and chronic schistosomiasis, hepatitis and various types of cutaneous and systemic vasculitis, utilizing two highly sensitive radioimmunoassays for detecting immune complexes, i.e. 125I-Clq binding assay and the Raji cell radioimmunoassay. We have developed a new, sensitive radioimmunoassay for the detection of IgA containing immune complexes. We have determined the antibody classes present in the immune complexes and examined the physiochemical characteristics of these complexes, as well as the reaction of these complexes with mediators of inflammation such as the complement system. We have examined the correlation between absolute levels of circulating immune complexes, the extent and severity of clinical disease, and reticuloendothelial system function. We have also examined the influence that certain genes of the major histocompatibility complex exert on immune function in vivo and in vitro in humans.